chr6-169240637-A-C

Variant names:

• chr6-169240637-A-C
• rs13192849
• NM_003247.5:c.892-45T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003247.5(THBS2):​c.892-45T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,587,562 control chromosomes in the GnomAD database, including 7,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2716 hom., cov: 33)
  • Exomes 𝑓: 0.054 (4390 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 3 publications found

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	NM_003247.5	MANE Select	c.892-45T>G		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.892-45T>G		intron	N/A	NP_001368868.1
	THBS2	NM_001381942.1		c.661-45T>G		intron	N/A	NP_001368871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	ENST00000617924.6	TSL:1 MANE Select	c.892-45T>G		intron	N/A	ENSP00000482784.1
	THBS2	ENST00000366787.7	TSL:1	c.892-45T>G		intron	N/A	ENSP00000355751.3
	THBS2-AS1	ENST00000444188.3	TSL:3	n.2152A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20722 AN: 152130 Hom.: 2712 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.0841 AC: 20253 AN: 240894 AF XY: 0.0771

Gnomad AFR exome AF: 0.356

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.0577

Gnomad NFE exome AF: 0.0389

Gnomad OTH exome AF: 0.0714

GnomAD4 exome AF: 0.0536 AC: 76921 AN: 1435314 Hom.: 4390 Cov.: 29 AF XY: 0.0526 AC XY: 37388 AN XY: 710176

African (AFR) AF: 0.360 AC: 11848 AN: 32914

American (AMR) AF: 0.102 AC: 4400 AN: 42972

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 919 AN: 25516

East Asian (EAS) AF: 0.184 AC: 7192 AN: 38988

South Asian (SAS) AF: 0.0531 AC: 4420 AN: 83272

European-Finnish (FIN) AF: 0.0561 AC: 2958 AN: 52728

Middle Eastern (MID) AF: 0.0574 AC: 326 AN: 5676

European-Non Finnish (NFE) AF: 0.0371 AC: 40639 AN: 1094056

Other (OTH) AF: 0.0713 AC: 4219 AN: 59192

GnomAD4 genome AF: 0.136 AC: 20758 AN: 152248 Hom.: 2716 Cov.: 33 AF XY: 0.134 AC XY: 10011 AN XY: 74446

African (AFR) AF: 0.345 AC: 14323 AN: 41498

American (AMR) AF: 0.0899 AC: 1375 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3472

East Asian (EAS) AF: 0.185 AC: 960 AN: 5176

South Asian (SAS) AF: 0.0536 AC: 259 AN: 4832

European-Finnish (FIN) AF: 0.0620 AC: 658 AN: 10620

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2707 AN: 68030

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.0902 Hom.: 306

Bravo AF: 0.150

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.10
DANN	Benign	0.51
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13192849; hg19: chr6-169640732; COSMIC: COSV64677758; COSMIC: COSV64677758;